Key result
APOE ε4 genotype did not significantly interact with lifestyle risk factors to worsen cognitive abilities, but rather showed a direct outright association with worse cognitive ability.
Why the study?
The study was conducted to test for interactions between APOE epsilon4 genotype and lifestyle factors on worse cognitive abilities.
Does APOE ε4 genotype interact with lifestyle factors to worsen cognitive abilities in the general population?
Cohort (n=326,535)
Yes
Does APOE ε4 genotype interact with lifestyle factors to worsen cognitive abilities in the general population?
p-value: p=>0.05
APOE ε4 genotype is directly associated with worse cognitive ability, but does not appear to increase vulnerability to the negative effects of lifestyle risk factors.
APOE ε4 directly associates with worse cognition without lifestyle interaction; hypothesis-generating and requires prospective validation before informing risk stratification.
Objective To test for interactions between APOE ε4 genotype and lifestyle factors on worse cognitive abilities in UK Biobank. Methods Using UK Biobank cohort data, we tested for interactions between APOE ε4 allele presence, lifestyle factors of alcohol intake, smoking, total physical activity and obesity, and sex, on cognitive tests of reasoning, information processing speed, and executive function (n range = 70,988–324,725 depending on the test). We statistically adjusted for potential confounders of age, sex, deprivation, cardiometabolic conditions, and educational attainment. Results There were significant associations between APOE ε4 and worse cognitive abilities, independent of potential confounders, and between lifestyle risk factors and worse cognitive abilities; however, there were no interactions at multiple correction-adjusted p < 0.05, against our hypotheses. Conclusions Our results do not provide support for the idea that ε4 genotype increases vulnerability to the negative effects of lifestyle risk factors on cognitive ability, but rather support a primarily outright association between APOE ε4 genotype and worse cognitive ability.
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Lyall et al. (2019) conducted a cohort in Cognitive decline (n=326,535). APOE ε4 genotype and lifestyle factors vs. APOE ε4 absent was evaluated on Interaction between APOE ε4 genotype and lifestyle factors on cognitive abilities (p=>0.05). APOE ε4 genotype did not significantly interact with lifestyle risk factors to worsen cognitive abilities, but rather showed a direct outright association with worse cognitive ability.
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